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Wu H.,Hubei University | Liu S.,Wuhan University | Gong J.,Hubei University | Liu J.,Hubei University | And 5 more authors.
Cancer Letters | Year: 2017

Gastric carcinoma is a common malignant disease worldwide and has a dismal prognosis. Doxorubicin (DOX), one of the most widely used chemotherapeutic agents, has limited use because of its side effects and the development of tumor-cell resistance. Combinations of doxorubicin and non-cross-resistant agents have been required for adjuvant chemotherapy of gastric cancer. Here, we report that VCPA, a novel synthetic derivative of α-Tocopheryl Succinate, induced apoptosis via production of reactive oxygen species (ROS). When used in combination with doxorubicin, lower doses of VCPA sensitized human gastric cancer cells to DOX-induced apoptosis. The DOX/VCPA combination treatment caused an imbalance in the ratio of Bcl-2 to Bax and induced a lethal mitochondrial dysfunction. MAPKs were also activated in response to the DOX/VCPA treatment but played a protective role in DOX-induced cell death. In vivo studies further confirmed the sensitizing effect of VCPA. Combining DOX with VCPA markedly inhibited tumor growth in a tumor xenograft model of human gastric cancer. Taken together, our study revealed that VCPA, through increased ROS production, could synergize with DOX and circumvent DOX resistance in human gastric cancer cells. © 2017 Elsevier B.V.


Chen C.,Wuhan University | Chen C.,Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center | Xia H.-S.,Hubei Cancer Hospital | Gong Y.-P.,Hubei Cancer Hospital | And 10 more authors.
Biomaterials | Year: 2010

Accurate classification is fundamental for breast cancer (BC) personalized care. Current BC classification based on the either traditional morphological staging or molecular signatures seems inefficient to reveal the" true" behaviors of invasive BC evolution. An appropriate approach combining the macro- and micro-pathologic information might be more useful academically as well as clinically. Here we explore a holistic approach by integrating a key molecular prognostic indicator of BC, HER2, with quantitative determination using quantum dots (QDs)-based nanotechnology and spectral analysis, and a key macropathologic indicator, tumor size, resulting a new indicator, total HER2 load. This indicator might better reveal BC heterogeneity and new subtypes of BC with different 5-year disease-free survival compared with current methods, which could be helpful in formulating a more personalized targeted therapy for BC. Furthermore, this mode integrating macro- and micro-pathological indicators might help gain new insights into invasive BC biological behaviors. © 2010 Elsevier Ltd.


Al Zobair A.A.,Wuhan University | Al Zobair A.A.,Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center | Al Obeidy B.F.,Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center | Yang L.,Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center | And 7 more authors.
Medical Journal of Wuhan University | Year: 2012

Objective: To study the relationship between EGFR and CXCR4 in non-small cell lung cancer cell line A549. Methods: Serum-starved A549 cells were stimulated with different concentration of EGF (20 μg/L, 40 μg/L, and 60 μg/L) for 24 hours and then CXCR4 expression levels were evaluated by real time PCR. Serum starved A549 cells were treated with AG1478 (specific inhibitor of EGFR phosphorylation) (10 μmol/L) for 24 h, CXCR4 expression were re-evaluated by real-time PCR and Western blot. Serum-starved A549 cells were treated with EGF in the presence or absence of LY294002 (PI-3 kinase pathway inhibitor) to investigate the changes of CXCR4 mRNA levels. Results: EGF up-regulated CXCR4 expression about 3 to 4 folds. CXCR4 expression was reduced after treatment with EGFR phosphorylation inhibitor (AG1478). EGF induced up-regulation of CXCR4 is enhanced through PI-3 kinase pathway, and CXCR4 mRNA up-regulation increased in a concentration-dependant manner. Conclusion: EGF up-regulates the CXCR4 expression through PI-3K signaling pathway, and this interaction between CXCR4 and EGFR intracellular signaling pathways may contribute to tumor progression. Inhibition of both EGFR and CXCR4 may be potential therapeutic targets for NSCLC patients who have concomitant over expression of CXCR4 and EGFR.


Chen C.,Wuhan University | Chen C.,Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center | Sun S.-R.,Renmin University of China | Gong Y.-P.,Hubei Cancer Hospital | And 14 more authors.
Biomaterials | Year: 2011

The emerging molecular breast cancer (BC) classification based on key molecules, including hormone receptors (HRs), and human epidermal growth factor receptor 2 (HER2) has been playing an important part of clinical practice guideline. The current molecular classification mainly based on their fingerprints, however, could not provide enough essential information for treatment decision making. The molecular information on both patterns and quantities could be more helpful to heterogeneities understanding for BC personalized medicine. Here we conduct quantitative determination of HRs and HER2 by quantum dots (QDs)-based quantitative spectral analysis, which had excellent consistence with traditional method. Moreover, we establish a new molecular classification system of BC by integrating the quantitative information of HER2 and HRs, which could better reveal BC heterogeneity and identify 5 molecular subtypes with different 5-year prognosis. Furthermore, the emerging 5 molecular subtypes based on simple quantitative molecules information could be as informative as multi-genes analysis in routine practice, and might help formulate a more personalized comprehensive therapy strategy and prognosis prediction. © 2011 Elsevier Ltd.


Liu X.-L.,Wuhan University | Liu X.-L.,Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center | Peng C.-W.,Wuhan University | Peng C.-W.,Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center | And 12 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

It has been well recognized that human epidermal growth factor receptor 2 (HER2) level in breast cancer (BC) is closely related to the malignant biologic behaviors of the tumor, including invasion and metastasis. Yet, there has been a lack of directly observable evidence to support such notion. Here we report a quantum dots (QDs)-based double-color imaging technique to simultaneously show the HER2 level on BC cells and the type IV collagen in the tumor matrix. In benign breast tumor, the type IV collagen was intact. With the increasing of HER2 expression level, there has been a progressive decrease in type IV collagen around the cancer nest. At HER2 (3+) expression level, there has virtually been a total destruction of type IV collagen. Moreover, HER2 (3+) BC cells also show direct invasion into the blood vessels. This novel imaging method provides direct observable evidence to support the theory that the HER2 expression level is directly related to BC invasion. © 2011 Elsevier Inc.

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